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Updated: May 10, 2026
09:34
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Mutations in LRPAP1 are associated with severe myopia in humans
Mohammed A Aldahmesh1, Arif O Khan, Hisham Alkuraya
1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
American Journal of Human Genetics
|July 9, 2013
Summary
Genetic analysis identified mutations in LRPAP1 and CTSH genes causing isolated myopia in families. These findings reveal new molecular mechanisms underlying myopia, a common vision disorder.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- Myopia is a prevalent eye condition with poorly understood isolated form pathogenesis.
- Genetic predisposition to myopia is evident, yet identifying specific genetic risk factors remains challenging.
Purpose of the Study:
- To identify genetic mutations responsible for isolated myopia in consanguineous families.
- To elucidate novel molecular pathways involved in myopia development.
Main Methods:
- Exome and autozygome analysis were performed on four consanguineous families with myopia.
- Identified homozygous truncating variants in LRPAP1 and CTSH genes.
- Analyzed LRP1 and TGF-β activity in affected individuals' cells and studied murine CTSH ortholog deficiency.
Main Results:
- Identified homozygous truncating variants in LRPAP1 and CTSH as likely causal mutations for isolated myopia.
- Observed LRP1 deficiency and TGF-β upregulation in cells from affected individuals.
- Demonstrated that CTSH deficiency in mice leads to abnormal globe development, mirroring the human phenotype.
Conclusions:
- LRPAP1 and CTSH play a significant role in the genetics of isolated myopia.
- Mendelian forms of myopia are powerful tools for uncovering molecular mechanisms relevant to common myopia phenotypes.
- Findings suggest a link between LRPAP1, CTSH, TGF-β signaling, and scleral remodeling in myopia pathogenesis.
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